Genetic Variant NM_006089.3:c.1036G>A (chrX-18260204-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_006089.3(SCML2):c.1036G>A(p.Ala346Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000492 in 1,198,239 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 15 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., 3 hem., cov: 22)

Exomes 𝑓: 0.000047 ( 0 hom. 12 hem. )

Consequence

SCML2
NM_006089.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -5.32

Publications

1 publications found

Variant links:

Genes affected

SCML2 (HGNC:10581): (Scm polycomb group protein like 2) This gene encodes a member of the Polycomb group proteins. These proteins form the Polycomb repressive complexes which are involved in transcriptional repression. The encoded protein binds histone peptides that are monomethylated at lysine residues and may be involved in regulating homeotic gene expression during development. [provided by RefSeq, Jun 2010]

SCML2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04089734).

BS2

High Hemizygotes in GnomAd4 at 3 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006089.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCML2	NM_006089.3	MANE Select	c.1036G>A	p.Ala346Thr	missense	Exon 9 of 15	NP_006080.1	Q9UQR0-1
	SCML2	NR_033717.2		n.1157G>A		non_coding_transcript_exon	Exon 9 of 16

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SCML2	ENST00000251900.9	TSL:1 MANE Select	c.1036G>A	p.Ala346Thr	missense	Exon 9 of 15	ENSP00000251900.4	Q9UQR0-1
SCML2	ENST00000926833.1		c.1036G>A	p.Ala346Thr	missense	Exon 9 of 15	ENSP00000596892.1
SCML2	ENST00000926834.1		c.1036G>A	p.Ala346Thr	missense	Exon 10 of 16	ENSP00000596893.1

Frequencies

GnomAD3 genomes

AF:

0.0000722

AC:

AN:

110797

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000164

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000194

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000223

AC:

AN:

179609

AF XY:

0.0000156

show subpopulations

Gnomad AFR exome

AF:

0.0000770

Gnomad AMR exome

AF:

0.0000375

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000248

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000469

AC:

AN:

1087442

Hom.:

Cov.:

AF XY:

0.0000339

AC XY:

AN XY:

354160

show subpopulations

African (AFR)

AF:

0.000306

AC:

AN:

26183

American (AMR)

AF:

0.0000286

AC:

AN:

34980

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19192

East Asian (EAS)

AF:

0.00

AC:

AN:

30097

South Asian (SAS)

AF:

0.0000567

AC:

AN:

52942

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40352

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4095

European-Non Finnish (NFE)

AF:

0.0000396

AC:

AN:

833956

Other (OTH)

AF:

0.000131

AC:

AN:

45645

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.426

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000722

AC:

AN:

110797

Hom.:

Cov.:

AF XY:

0.0000907

AC XY:

AN XY:

33073

show subpopulations

African (AFR)

AF:

0.000164

AC:

AN:

30457

American (AMR)

AF:

0.000194

AC:

AN:

10306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2635

East Asian (EAS)

AF:

0.00

AC:

AN:

3559

South Asian (SAS)

AF:

0.00

AC:

AN:

2604

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5775

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.0000188

AC:

AN:

53052

Other (OTH)

AF:

0.00

AC:

AN:

1489

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000907

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-1.2

CADD

Benign

0.0010

(source)

DANN

Benign

0.69

DEOGEN2

Benign

0.025

FATHMM_MKL

Benign

0.0011

LIST_S2

Benign

0.33

M_CAP

Benign

0.0019

MetaRNN

Benign

0.041

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.69

PhyloP100

-5.3

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.79

REVEL

Benign

0.016

Sift

Benign

0.35

Sift4G

Benign

0.45

Polyphen

0.0020

Vest4

0.031

MVP

0.043

MPC

0.57

ClinPred

0.098

GERP RS

-9.1

Varity_R

0.045

gMVP

0.17

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over